T-cell Immunity and Probiotics
Last newsletter we promised to explain a very scientific looking chart to you. This newsletter we're going to do just that. Please be warned: This newsletter may be "hard to swallow", but once you "digest it", (sorry couldn't resist!) you'll practically have a degree in biology! ; - )
T-cell lymphocytes are born in the bone marrow and educated in the thymus where they graduate as naïve T-cells (Tn cells). Upon interaction with dendritic cells (DC cells) they become one of three types of T-cells: Th1, Th2 or Treg.
Specific cytokines secreted by the DCs create these T-cell types: IL-12 creates a Th1 cell, IL-4 creates a Th2 cell, and IL-2 a Treg cell. What DC cells encounter determines the type of T-cell they create: For an encounter with a bacterial pathogen such as Salmonella a Th1 cell is created; for an encounter with foreign matter in the blood a Th2 cell is created; Treg cells are created when it’s necessary to calm down the immune response.
Most of these interactions occur in gut epithelial tissue which heralds the importance of maintaining gut surfaces in a healthy condition. Creating a healthy gut surface is one mechanism by which probiotics benefit T-cell immunity: Intestinal surfaces colonized with Lactobacillus and Bifidobacterium strains protect epithelial tissue (villi and microvilli) by competitive exclusion, they don’t allow pathogens to occupy the same space they occupy.
Colonized probiotics then send out “all is clear” messages that modulate dendritic cell responses preventing negative hyperactivity – see The Probiotics Revolution, Gary B. Huffnagle, Ph.D., Bantam Books, 2007.
Fig. 1. below. If the dendritic cells are the head coaches the T-cells are the Quarterbacks of the immune system; there are many games playing during an infection-fight so multiple coaches and players are required – millions of them. The passes the T-cells throw are molecule messages, cytokines that activate the immune processes. The Th1 cells (T helper 1) cells are involved with CELLULAR IMMUNITY, they work in the spaces between cells.
By producing cytokines INF-gamma and TNF alpha the Th1 cells command macrophages to turn on and a pathogenic invader is killed by phagocytosis (macrophages engulf and digest the pathogen). This is an inflammatory process but a critical first line of defense.
The Lactobacillus acidophilus LA-1 (also called NCFM) strain in Theralac® stimulates the production of INF-gamma and TNF-alpha which enhances the Th1 response – see Food Protection, 2000, 63(5): 638-644.
The Th2 cells (T helper 2) are involved with HUMORAL IMMUNITY, they direct white blood cells called B-cells to produce antibodies in response to foreign matter in the blood. Such foreign matter may be virus particles, microbial toxins, food antigens, strange proteins, pieces of dead bacteria, etc. The antibody-antigen complexes that result can then be disposed by macrophages and other phagocytes. This occurs in the blood or lymph (humoral) streams.
Th2 cells activate the B-cells by excreting cytokines IL-4 or IL-5 (IL stands for Interlukin). This is a non-inflammatory process – a critical second line of defense. When things are going right an infection is defeated by a balanced Th1 + Th2 attack. The Th2 cells also produce IL-10 as do Treg cells (T regulatory cells) which calms down the Th1 response as an infection nears defeat. IL-10 production is an extremely important process: The Bifidobacterium lactis BL-34 (also called Bl-04) in Theralac® increases the production of IL-10 – see World Journal of Gastroenterology, 2007, 13(2): 236-243.
Balance is the key to proper operation of T-cell immunity. As you can see in Figure #1 the Th1 cytokines counteract Th2 development and, vice versa, the IL-10 produced by Th2 cells inhibits Th1 cytokines.
Many factors can throw this mutual counteraction out of whack. The right combination of probiotic strains can help insure that balance is maintained. Both probiotic strains discussed above, LA-1 and BL-34, are present in Theralac® at 10 billion CFU per capsule (and are supported by 10 billion CFU of three other probiotic strains for a total of 30 billion CFU/capsule) – see www.theralac.com. Therefore, this formulation has a balancing effect on the Th1 and Th2 response since each strain supports one side over the other.
This is the second mechanism by which probiotics benefit T-cell immunity >> they help insure a balanced attack.
When balance fails and the T-cell scale tips to one side or the other – see the balancing triangle in the center of Figure #1 – tissue damage and/or various diseases result. If the scale tips in favor of Th1 responses, and this becomes chronic, autoimmune diseases such as Crohns, rheumatoid arthritis and MS can result.
When the scale tips toward Th2 responses that become chronic, atopic diseases such asthma, hay fever and food allergies develop.
The LA-1 strain in Theralac® can offset the body’s Th2 tendency to over respond to innocuous substances in the blood by enhancing the production of IgA – which modulates such activity – see Journal of Dairy Science, 1999, 82: 649-660.
This, then, is a third mechanism for probiotics. T-cell immunity is quite complicated and immunologists have added considerable detail to what I have presented above. For example, there are more cytokines involved than what are shown.
Treg cells are now subdivided into several categories with different functions. Some references talk about Th3 cell involvement. Other phagocytes such as neutrophils and N. K. killer cells support the macrophage response and mast cells and eosinophils support the B-Cells.
A dendritic cell's state of maturity determines its orientation, Th1 vs Th2. Tn cells may appear in various stages of activation prior to becoming a Th1 or Th2. The above description is meant to encompass the major functioning parameters of T-cell immunity in a form that fits on one page and allows for a discussion on how probiotics interact in a complimentary manner.
This is a dynamic field where more research is needed.
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